Cabozantinib Plus Atezolizumab or Cabozantinib Alone in Patients With Advanced NSCLC Previously Treated With an Immune Checkpoint Inhibitor: Results From the Phase 1b COSMIC-021 Study

Joel W. Neal, MD, PhD; Armando Santoro, MD; Maria Gonzalez-Cao, MD, PhD; Farah Louise Lim, MRCP, MD; Bruno Fang, MD; Ryan D. Gentzler, MD, MS; Jerome Goldschmidt, MD; Polina Khrizman, MD; Claudia Proto, MD; Shiven Patel, MD, MBA, FACP; Sonam Puri, MD; Stephen V. Liu, MD; Erminia Massarelli, MD, PhD, MS; Denise Williamson, MPH; Martin Schwickart, PhD; Christian Scheffold, MD, PhD; Svetlana Andrianova, MD, MPH; Enriqueta Felip, MD, PhD

JTO Clinical and Research Reports (Oct 2024)

Cabozantinib Plus Atezolizumab or Cabozantinib Alone in Patients With Advanced NSCLC Previously Treated With an Immune Checkpoint Inhibitor: Results From the Phase 1b COSMIC-021 Study

Joel W. Neal, MD, PhD,
Armando Santoro, MD,
Maria Gonzalez-Cao, MD, PhD,
Farah Louise Lim, MRCP, MD,
Bruno Fang, MD,
Ryan D. Gentzler, MD, MS,
Jerome Goldschmidt, MD,
Polina Khrizman, MD,
Claudia Proto, MD,
Shiven Patel, MD, MBA, FACP,
Sonam Puri, MD,
Stephen V. Liu, MD,
Erminia Massarelli, MD, PhD, MS,
Denise Williamson, MPH,
Martin Schwickart, PhD,
Christian Scheffold, MD, PhD,
Svetlana Andrianova, MD, MPH,
Enriqueta Felip, MD, PhD

Affiliations

Joel W. Neal, MD, PhD: Division of Oncology, Stanford Cancer Institute, Palo Alto, California; Corresponding author. Address for correspondence: Joel W. Neal, MD, PhD, Stanford Cancer Institute, 875 Blake Wilbur Drive, Palo Alto, California 94304.
Armando Santoro, MD: Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital- Humanitas Cancer Center, Rozzano, Milan, Italy
Maria Gonzalez-Cao, MD, PhD: Translational Cancer Research Unit, Instituto Oncologico Dr Rosell, Dexeus University Hospital, Barcelona, Spain
Farah Louise Lim, MRCP, MD: Barts Health NHS Trust, St Bartholomew’s Hospital, London, United Kingdom
Bruno Fang, MD: Astera Cancer Care, East Brunswick, New Jersey
Ryan D. Gentzler, MD, MS: Division of Hematology Oncology, University of Virginia Cancer Center, Charlottesville, Virginia
Jerome Goldschmidt, MD: Department of Medical Oncology, Blue Ridge Cancer Care, Blacksburg, Virginia
Polina Khrizman, MD: MD Anderson Cancer Center at Cooper, Camden, New Jersey
Claudia Proto, MD: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
Shiven Patel, MD, MBA, FACP: Division of Medical Oncology, The Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah
Sonam Puri, MD: Division of Medical Oncology, The Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah
Stephen V. Liu, MD: Georgetown Lombardi Comprehensive Cancer Center, Washington, District of Columbia
Erminia Massarelli, MD, PhD, MS: Department of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California
Denise Williamson, MPH: Department of Biostatistics, Exelixis Inc, Alameda, California
Martin Schwickart, PhD: Department of Translational Medicine, Exelixis Inc, Alameda, California
Christian Scheffold, MD, PhD: Department of Clinical Development, Exelixis Inc, Alameda, California
Svetlana Andrianova, MD, MPH: Department of Clinical Development, Exelixis Inc, Alameda, California
Enriqueta Felip, MD, PhD: Medical Oncology Service, Vall d’Hebron Institute of Oncology (VIHO), Vall d’Hebron Barcelona Hospital Campus, Universitat Autonoma de Barcelona, Barcelona, Spain

Journal volume & issue: Vol. 5, no. 10
p. 100666

Abstract

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Introduction: We evaluated efficacy and safety of cabozantinib plus atezolizumab or cabozantinib alone in advanced NSCLC previously treated with an immune checkpoint inhibitor (ICI). Methods: COSMIC-021 (NCT03170960) is a phase 1b, multicenter study in advanced solid tumors. This analysis included patients with stage IV non-squamous NSCLC without actionable genomic aberrations in EGFR, ALK, ROS1, or BRAF-V600E who progressed on one prior ICI and less than or equal to two prior lines of systemic anticancer therapy. Patients received cabozantinib 40 mg orally/day plus atezolizumab 1200 mg intravenously every three weeks (combination cohort) or cabozantinib 60 mg orally/day (single-agent cabozantinib cohort). Primary end point of the combination cohort was objective response rate per Response Evaluation Criteria in Solid Tumors v1.1 by investigator. Outcomes in the single-agent cabozantinib cohort were exploratory. Results: Eighty-one patients assigned to combination therapy and 31 assigned to single-agent cabozantinib received greater than or equal to one dose of study treatment. Median (range) follow-up was 26.1 months (12.1–44.2) and 22.4 months (1.5–29.0), respectively. Objective response rate was 20% (95% confidence interval: 11.7%–30.1%) in combination cohort and 6% (95% confidence interval: 0.8%–21.4%) in single-agent cabozantinib cohort. Treatment-related adverse events (TRAEs) occurred in 86% of patients in the combination cohort and 90% in the single-agent cabozantinib cohort; grade 3/4 TRAEs were 44% and 48%, respectively. There were two grade 5 TRAEs: pneumonitis (n = 1, combination) and gastric ulcer hemorrhage (n = 1, single-agent). Neither PD-L1 expression in tumor cells nor tumor mutation burden correlated with outcomes. Conclusions: Cabozantinib plus atezolizumab demonstrated modest clinical activity and manageable toxicity in advanced NSCLC after progression on prior ICI.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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